The gal-lectin in host defence against entamoeba histolytica

溶组织内阿米巴是一种寄生原虫，可引起阿米巴病，其特征是出血性痢疾和肝脓肿。世界上大约1%的人口携带这种寄生虫，每年造成5000万例侵袭性疾病和10万人死亡。它是全球十大主要死亡原因之一。目前尚不清楚为什么寄生虫在感染期间没有得到控制。然而，被药物治愈的患者对再次侵袭具有抵抗力，这表明保护性免疫发生了。临床和实验研究表明，由巨噬细胞（杀死寄生虫的白细胞）介导的细胞介导免疫在控制和抵抗再感染中起重要作用。因此，控制阿米巴病的首要任务是研制安全有效的疫苗。参与疾病起始的寄生虫的主要表面分子是称为半乳糖凝集素的半乳糖结合蛋白。该蛋白具有免疫优势，可被患有此病的患者的血清识别。用gal凝集素免疫动物可保护动物免受侵袭性感染，提示它是一种很好的阿米巴病疫苗候选分子。然而，目前尚不清楚gal凝集素的哪一部分引起保护性免疫反应。我们假设凝集素的特定部分刺激细胞介导的免疫，以防御宿主疾病。因此，本研究的具体目的是：(1)确定gal -凝集素刺激先天免疫和适应性免疫反应的关键区域；(2)确定宿主细胞受体和参与保护性免疫的信号传导事件。我们的策略是首先使用一组识别不同结构域的单克隆抗体精细绘制gal凝集素的保护性表位。其次，我们将识别树突状细胞上的受体，通过使用缺乏gal -凝集素假定受体的细胞和动物来刺激保护性免疫反应。表征受体和参与刺激正确免疫反应的信号事件对于制定战略以加强针对这一毁灭性疾病的疫苗开发具有重要意义。

Entamoeba histolytica is a parasitic protozoan that causes the disease amebiasis characterized by bloody dysentery and liver abscess. About 1% of the world's population carries the parasite, resulting in 50 million cases of invasive disease and 100,000 deaths per year. It is among the 10 leading causes of mortality worldwide. At present, it is not known why the parasites are not controlled during infection. However, patients who are drug-cured are resistant to reinvasion suggesting that protective immunity occurs. Clinical and experimental studies indicate that cell-mediated immunity mediated by macrophages (the white blood cells that kill the parasites) is important in control and resistance to re-infection. Thus, a priority to the control of amebiasis is to develop a safe and effective vaccine. The major surface molecule on the parasite involved in the initiation of disease is the galactose-binding protein called the Gal-lectin. This protein is immunodominant and is recognized by serum from patients who had/has the disease. Immunization of animals with the Gal-lectin protected them against a challenge infection suggesting it is a good vaccine candidate molecule against amebiasis. However, it is not known what portion(s) of the Gal-lectin elicits the protective immune response. We hypothesized that specific portions of the Gal-lectin stimulates cell-mediated immunity for host defense against the disease. Accordingly, the specific aims of this study are: (1) to identify the critical regions of the Gal-lectin that stimulate innate and adaptive immune responses and, (2) to identify the host cell receptor and the signaling events involved in protective immunity. Our strategy is to first fine map the protective epitopes of the Gal-lectin using a panel of monoclonal antibodies that recognize distinct domains. Secondly, we will identify the receptors on dendritic cells that stimulate a protective immune response by using cells and animals that are deficient in the putative receptor(s) for the Gal-lectin. Characterizing the receptor and the signaling events involved in stimulating the right immune response is important in developing strategies to enhance vaccine development against this devastating disease.